The purpose of the proposed research is to gain an understanding of the factors which regulate the release of renin from the kidney and from isolated secretory granules in both normal and pathological conditions. The experimental approach will utilize rat kidney slices and isolated granules and this will eliminate some variables such as nervous or vascular control of renin release. Spontaneous and induced release of renin will be examined using preparations from normal animals, hypertensive animals, and animals on high or low sodium diets. Emphasis will be on analyzing the role of calcium and energy metabolism in spontaneous and drug-induced release. Variables to be examined on isolated granules include ions, adenine nucleotides, pH, osmotic strength and temperature. These types of studies have been employed previously in delineating the cellular mechanisms involved in the release of the secretory substances (stimulus-secretion coupling). It is hoped that this combined approach to studying renin release (intact cells and isolated granules) will provide a useful insight into the control of renin release with implications for normal, pathological and drug-induced states.